chr6-129313110-G-A

Variant names:

• chr6-129313110-G-A
• rs3798663
• NM_000426.4:c.3411+13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.3411+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,520,938 control chromosomes in the GnomAD database, including 30,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6769 hom., cov: 33)
  • Exomes 𝑓: 0.16 (23802 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.05
• Publications: 9 publications found

Genes affected

LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

LAMA2 Gene-Disease associations (from GenCC):

• congenital merosin-deficient muscular dystrophy 1A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Myriad Women’s Health
• LAMA2-related muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy, limb-girdle, autosomal recessive 23

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-129313110-G-A is Benign according to our data. Variant chr6-129313110-G-A is described in ClinVar as Benign. ClinVar VariationId is 92951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.3411+13G>A		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.3411+13G>A		intron	N/A	NP_001073291.2	A0A087WYF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.3411+13G>A		intron	N/A	ENSP00000400365.2	P24043
	LAMA2	ENST00000618192.5	TSL:5	c.3675+13G>A		intron	N/A	ENSP00000480802.2	A0A087WX80
	LAMA2	ENST00000617695.5	TSL:5	c.3411+13G>A		intron	N/A	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38619 AN: 151972 Hom.: 6752 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.222 AC: 52098 AN: 234696 AF XY: 0.209

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.162 AC: 221945 AN: 1368848 Hom.: 23802 Cov.: 21 AF XY: 0.161 AC XY: 109445 AN XY: 679364

African (AFR) AF: 0.469 AC: 14764 AN: 31494

American (AMR) AF: 0.334 AC: 13888 AN: 41630

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3698 AN: 24238

East Asian (EAS) AF: 0.547 AC: 21285 AN: 38938

South Asian (SAS) AF: 0.181 AC: 14634 AN: 80898

European-Finnish (FIN) AF: 0.152 AC: 8014 AN: 52576

Middle Eastern (MID) AF: 0.217 AC: 1185 AN: 5462

European-Non Finnish (NFE) AF: 0.129 AC: 133712 AN: 1036740

Other (OTH) AF: 0.189 AC: 10765 AN: 56872

GnomAD4 genome AF: 0.254 AC: 38680 AN: 152090 Hom.: 6769 Cov.: 33 AF XY: 0.258 AC XY: 19201 AN XY: 74372

African (AFR) AF: 0.461 AC: 19105 AN: 41464

American (AMR) AF: 0.291 AC: 4445 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2797 AN: 5146

South Asian (SAS) AF: 0.209 AC: 1011 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1568 AN: 10598

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8452 AN: 67990

Other (OTH) AF: 0.242 AC: 511 AN: 2112

Alfa AF: 0.211 Hom.: 1202

Bravo AF: 0.280

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Merosin deficient congenital muscular dystrophy (2)
-	-	1	Congenital muscular dystrophy due to partial LAMA2 deficiency (1)
-	-	1	LAMA2-related muscular dystrophy (1)
-	-	1	Muscular dystrophy, limb-girdle, autosomal recessive 23 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.22
DANN	Benign	0.56
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3798663; hg19: chr6-129634255; COSMIC: COSV70347843;